[Summary text]
Study design: Randomized controlled trial
Study grouping: Parallel group
Baseline Characteristics
Intervention
Control
Overall
Included criteria: Patients who were diagnosed with dementia in Alzheimer’s disease, vascular dementia, or a mixture of Alzheimer’s disease and vascular dementia (as defined by ICD-10 (international classification of diseases, 10th revision, diagnostic criteria forresearch) were included; had been nursing home residents for more than four weeks; had a neuropsychiatric symptom; and were prescribed a selective serotonin reuptake inhibitor (escitalopram, citalopram, sertraline, or paroxetine) for at least three months.No changes in the dose of the current antidepressant treatment were allowed in the last four weeks before inclusionand throughout the study period. Changes in the prescription of psychotropic drugs other than antidepressants during the study period were allowed.
Excluded criteria: Disorder or schizophrenia, severe somatic disease or terminal illness, or an inability to take tablets or capsules as prescribed.The exclusion of people with a documented depressive disorder was based on interviews with the nursing home doctors as well as studying the patients’ medical records. Exclusion of patients with severe physical illness was based on ethical reasons and the assumption that they would not complete a study period of 25 weeks.
Pretreatment: No significant differences between the two groups at baseline, in terms of sex, age, the clinical dementia rating scale, dementia diagnosis, the Cornell scale, or the neuropsychiatric inventory were seen.
Intervention Characteristics
Intervention (Discontinuation group)
Control (Continuation group)
Depressive symptomer_Cornell scale (0-38)
BPSD_Neuropsychiatric inventory agitation total score
Kognitiv funktion_Severe impairment battery (SIB)(0-100)
Alvorlige bivirkninger (SAE)
Livskvalitet_Quality of life-Alzheimer's disease scale, patients' rating
Sponsorship source: The study was funded by unrestricted grants from the Innlandet Hospital Trust, the Research Council of Norway, and the South-Eastern Norway Regional Health Authority.
Country: Norway
Setting: Norwegian nursing homes; residents recruited by 16 study centres in Norway from August 2008 to June 2010.
Comments: Trial registration: ClinicalTrial.gov NCT00594269
Authors name: Sverre Bergh
Institution: Centre for Old Age Psychiatric Research, Innlandet Hospital Trust
Email: sverre.bergh@sykehuset-innlandet.no
Address: N-2312 Ottestad, Norway
Personer med demens og BPSD, men ikke depression. Skal have været i behandling med antidepressiva min. 3 mdr. Antidepressiva seponeres hos 63 og fortsættes hos 68. Opfølgning ved baseline, uge 4, 7, 13 og 25. Har flere relevante outcomes med (depressions-score, NPI, kognitiv funktion ved SIB og QoL), men kun data fra uge 25 præsenteres.
Study design: Randomized controlled trial
Study grouping: Parallel group
Baseline Characteristics
Overall
Included criteria: To be included, the patients had at least to be able to help in undressing and dressing themselves and in taking food (less than five points on items M1 and M2 of the Gottfries-Bråne-Sten (GBS) geriatric rating scale. The inclusion criteria further permitted only one of the following items to be scored six: orientation in space,orientation in time or personal orientation (items Ii, 12 and 13 of the GBS scale). The maximum score of recent and distant memory (14 and IS of the GBS scale) had to be four, while the minimum score of recent memory had to be two (mild to moderate disturbance).
Excluded criteria: Patients with severe dementia were not included.Patients who suffered from serious somatic illnesses (like cardiac decompensation and malignant arrhythmias, renal insufficiency, liver dysfunction, general gastrointestinal malabsorption, or disease of the haematopoietic system), those with a history of schizophrenia, epilepsy, alcoholismor drug dependence and those who had recently been treated with monoamine oxidase inhibitors were excluded.
Pretreatment: Significant differences at baseline in GBS-rating scale in Irritability (item 22) and Depressed mood (item 25), Figure 2.
Intervention Characteristics
Intervention
Control
No data available
Sponsorship source: Not reported
Country: Sweden, Norway and Finland
Setting: Hospitals and nursing home
Comments: The Ethical Committees of the various researchcentres and the national health authorities approved thesebiochemical investigations.
Authors name: Anna Lena Nyth
Institution: University of Göteborg, Department of Psychiatry and Neurochemistry
Email: not available
Address: St Jörgen's Hospital, S-422 03 Hisings-Backa, Sweden
Inkluderer 98 patienter med AD eller VD. Ekskluderer patienter med meget svær demens. Studiedesign: 1 uges 'wash-out', 4 uger med randomisering til placebo eller citalopram efterfulgt af 8 ugers openlabel behandling med citalopram. Til sidst randomiseres patienterne igen til placebo eller citalopram i 4 uger. Der rapporteres ikke om seponerings-symptomer i sidste fase. Det er beskrevet, at der i 'seponeringsfasen' både var forbedring og forværring på flere skalaer - men ingen data præsenteres.
Wrong study design
Wrong study design
Wrong patient population
Selection bias (biased allocation to interventions) due to inadequate generation of a randomised sequence
Quote: "We used computer generated randomisation (1:1) in blocks of four."
Quote: "The patients were then randomly assigned to double-blind treatment with either citalopram or placebo during four weeks."
Judgement Comment: It is unclear how the randomisation was performed Insufficient information about the sequence generation process
Selection bias (biased allocation to interventions) due to inadequate concealment of allocations prior to assignment
Quote: "Packing of study treatment was done at the Hospital Pharmacy at the Innlandet Hospital Trust, and was kept hidden, by the use of blank labels, from the participants, caregivers, and the assessors until the completion of data collection and statistical analyses. Randomisation was done across study"
Judgement Comment: No information provided
Performance bias due to knowledge of the allocated interventions by participants and personnel during the study
Quote: Randomisation and masking. We used computer generated randomisation (1:1) in blocks of four. Packing of study treatment was done at the Hospital Pharmacy at the Innlandet Hospital Trust, and was kept hidden, by the use of blank labels, from the participants, caregivers, and the assessors until the completion of data collection and statistical analyses. Randomisation was done across study centres"
Judgement Comment: Participants and personnel were blinded
Quote: "symptoms with a double-blind technique. With regard to drug administration, the patients received tablets of identical appearance each containing either 10mg citalopram or inactive substance. During the first two weeks"
Judgement Comment: No description of blinding of personnell. However it is assumed that the personnel were not aware of the containing of the tablets
Detection bias due to knowledge of the allocated interventions by outcome assessors
Quote: "Packing of study treatment was done at the Hospital Pharmacy at the Innlandet Hospital Trust, and was kept hidden, by the use of blank labels, from the participants, caregivers, and the assessors until the completion of data collection and statistical analyses. Randomisation was done across study centres and facilities."
Judgement Comment: Outcome assessors were blinded
Judgement Comment: The study is double blinded, but it is unclear if the outcome assessors are blinded
Attrition bias due to amount, nature or handling of incomplete outcome data
Quote: "We excluded 11 patients (four in the discontinuation group and seven in the continuation group) from the efficacy analyses, either because no post baseline assessments were available or because of study protocol violation; therefore, we included 117 patients for the efficacy analysis. Forty seven (37%) patients withdrew from the study prematurely, 28 (44%) in the discontinuation group and 19 (29%) in the continuation group. The only reason for drop outs that differed significantly between groups was an increase in neuropsychiatric symptoms, for 13 (21%) patients in the discontinuation group and four (6%) in the continuation group (table 2⇓).Efficacy analyses Table 3⇓ presents"
Judgement Comment: We included all patients in the safety analysis, and all patients with at least one assessment after the baseline (n=117) in the efficacy analysis. We analysed patients with complete data(n=81) for changes in the primary and secondary endpoints using analysis of covariance, presented as observed cases-
Judgement Comment: High risk due to incomplete data.
Judgement Comment: 9 participants withdrew from the study phase A and were not included in the efficacy analyses. 3 participants withdrew during phase B and C.
Reporting bias due to selective outcome reporting
Quote: "The trial was registered in ClinicalTrial.gov on 3 January 2008 (NCT00594269)." Data were assessed at baseline, four, seven, 13 and 25 weeks and only data from week 25 are reported and prespecified in the protocol.
Judgement Comment: No pre-specified protocol availaable
Bias due to problems not covered elsewhere in the table
Judgement Comment: The study appears to be free of other sources of bias
Judgement Comment: The study appears to be free of other sources of bias